OCTA Reliability — Clean Data

Session Information

current session info

─ Session info ───────────────────────────────────────────────────────────────
 setting  value                       
 version  R version 3.6.1 (2019-07-05)
 os       macOS High Sierra 10.13.6   
 system   x86_64, darwin15.6.0        
 ui       X11                         
 language (EN)                        
 collate  en_US.UTF-8                 
 ctype    en_US.UTF-8                 
 tz       America/Los_Angeles         
 date     2020-02-20                  

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[1] /Library/Frameworks/R.framework/Versions/3.6/Resources/library

Aim

The aim of this study is to obtain the Reliability estimates of the OCTA measurements.

Reliability incorporates:

• Repeatability - How reliable are repeated measures on the same day (Intra-Visit)

• Reproducibility - How reliable are repeated measures over multiple visits (Inter-Visit)

Data

This data was taken from a clean dataset that Jae emailed out on January 16th, 2020.

Jae organized the retina by six different methods. He created OCTA variable scores for the overall image, 2 hemifields, 4 quadrants, 6 sectors, 12 clock hours, and an annular ring.

Annular image scoring was also assessed, and ICC’s were similar, but slightly lower than global. Results for annular image scoring are not shown. For now, only the overall “global” image scoring will be shown.

Zeiss commercial vessel area density and flux variables are also shown for the global image scoring.

Note to Dom: The analysis was originally built with the global data. Towards the end of our work, we decided annulus would be a better data to use. I had already built the analysis using global data, so I just “trojan horsed” the annulus excel data into the global analysis that already exists. This is a bit of a hack, but saves an immense amount of time.

Data Wrangling

Rename Variables

This section will rename the variables to match the dictionary

Label Variables

This section will label variables appropriately.

Data Dictionary

Variable	Label
ptid	Patient Identification
Sociodemographic Variables
age	Age
female	Sex
Systemic Clinical Variables
htn_dx	Hypertension Diagnosis
dm_dx	Diabetes Mellitus Diagnosis
nro_dx	Optic Neuropathy
Ophthalmic Clinical Variables
dr_dx	Diabetic Retinopathy Diagnosis, Ordinal
dr_dx_bin	Diabetic Retinopathy Diagnosis, Binary
glc_sus_dx	Glaucoma Suspect Diagnosis
glc_dx	Glaucoma Diagnosis, Ordinal
glc_dx_bin	Glaucoma Diagnosis, Binary
glc_dx_bin_people	Glaucoma Diagnosis Laterality, Ordinal
OCT Angiography Variables
surg_proc_glaucoma	Surgical Procedure for Glaucoma
surg_proc_catextract	Surgical Procedure for Cataract Extraction
eyeid	Eye Identification
eye_imaged	Eye Imaged
time_stamp	Exam Date and Time
name_last	Last Name
name_first	First Name
image_area	Image Area
image_method	Image Method
image_size	Image Size
signal_strength	Signal Strength
v_diameter	Vessel Diameter (units?)
v_area_density	Vessel Area Density
v_skeleton_density	Vessel Skeleton Density (units?)
v_perimeter_index	Vessel Perimeter Index (units?)
v_complexity_index	Vessel Complexity Index (units?)
flow_impair_zone	Flow Impairment Zone (units?)
flux	Flux
zeiss_v_area_density	Vessel Area Density, Zeiss
zeiss_flux	Flux, Zeiss

Single Eye Participation

Venugopal (2019) et al. ran the analysis including all eyes.¹ Then they re-ran the analysis after selecting only a single eye randomly from each individual. They conclude minimal difference in the findings, and they report only the analysis that includes all eyes:

“The entire analysis was repeated considering one eye per subject (one eye was randomly chosen from subjects contributing both eyes for the primary analysis) and all the results were similar to the primary analysis.”¹

The following results are for a single eye—chosen at random—from each participant.

Later, towards the bottom of the analysis, the reliability statistics have been repeated for both eyes using linear mixed effects models.

Subsetting Cohorts

Intra-Visit Data

Intra-visit data was restricted to all measurements of the same eye that occurred on the same day. Some people had multiple measurements on multiple days. Their first day was included only.

Inter-Visit Data

Inter-visit data was restricted to the first measurement of the day for each eye. If a patient had their right eye measured:

• 3 times on Monday

• 5 times on Wednesday, and

• 2 times on Friday,

Then they would have three observations in this dataset:

• The first measurement from Monday,

• The first measurement from Wednesday, and

• The first measurement from Friday.

Data Flow Chart

This tallies how many participants, how many eyes, and how many measurements are included in the two data sets.

For repeatability statistics, normal and glaucoma groups may sum to greater than the total number of participants in the study because some participants have both eyes normal or both eyes with glaucoma, but some patients have unilateral glaucoma.

Both Eyes

dataset	n_participants	n_eyes	n_measurements
Annular Data - Intra-Visit - Both Eyes
Intra-Visit	149	244	644
Intra-Visit, Normal	73	118	321
Intra-Visit, Glaucoma	86	126	323
Annular Data - Inter-Visit - Both Eyes
Inter-Visit	148	243	628
Inter-Visit, Normal	72	117	256
Inter-Visit, Glaucoma	86	126	372
Annular Data - Inter-Visit - Both Eyes - Restrict 1 Year
Inter-Visit, 1 Year	103	165	401
Inter-Visit, 1 Year, Normal	44	69	143
Inter-Visit, 1 Year, Glaucoma	67	96	258
Annular Data - Inter-Visit - Both Eyes - Restrict 6 Months
Inter-Visit, 6 Months	67	107	254
Inter-Visit, 6 Months, Normal	23	32	68
Inter-Visit, 6 Months, Glaucoma	52	75	186

One Eye, Random

dataset	n_participants	n_eyes	n_measurements
Annular Data - Intra-Visit - One Eye, Random
Intra-Visit	149	149	382
Intra-Visit, Normal	68	68	180
Intra-Visit, Glaucoma	81	81	202
Annular Data - Inter-Visit - One Eye, Random
Inter-Visit	148	148	376
Inter-Visit, Normal	67	67	151
Inter-Visit, Glaucoma	81	81	225
Annular Data - Inter-Visit - One Eye, Random - Restrict 1 Year
Inter-Visit, 1 Year	102	102	246
Inter-Visit, 1 Year, Normal	40	40	85
Inter-Visit, 1 Year, Glaucoma	62	62	161
Annular Data - Inter-Visit - One Eye, Random - Restrict 6 Months
Inter-Visit, 6 Months	67	67	157
Inter-Visit, 6 Months, Normal	19	19	42
Inter-Visit, 6 Months, Glaucoma	48	48	115

Table 1: Summary Statistics

All table 1 data is shown, but publish only the Table 1 for the Intra-Visit.

For repeatability statistics, normal and glaucoma groups may sum to greater than the total number of participants in the study because some participants have both eyes normal or both eyes with glaucoma, but some patients have unilateral glaucoma.

Intra-Visit, Both Eyes OCTA Summary Statistics

Variables in intra-visit dataset

Intra-Visit

	Overall
n	149
Sociodemographic Variables
age (mean (SD))	56.97 (16.10)
Sex = Male (%)	72 (48.3)
Systemic Clinical Variables
Hypertension Diagnosis = Yes (%)	43 (28.9)
Diabetes Mellitus Diagnosis = Yes (%)	17 (11.4)
Optic Neuropathy = Yes (%)	1 ( 0.7)
Ophthalmic Clinical Variables
Glaucoma Diagnosis, Binary = Glaucoma (%)	76 (51.0)
Glaucoma Diagnosis Laterality, Ordinal (%)
Normal, Bilateral	60 (40.3)
Glaucoma, Bilateral	71 (47.7)
Glaucoma, Unilateral	18 (12.1)
Diabetic Retinopathy Diagnosis, Binary = Yes (%)	4 ( 2.7)
Ophthalmic Surgical Variables
Surgical Procedure for Cataract Extraction = Yes (%)	28 (18.8)
Surgical Procedure for Glaucoma (%)
None	103 (69.1)
Laser	24 (16.1)
Minimally Invasive Glaucoma Surgery	2 ( 1.3)
Filter	20 (13.4)
OCT Angiography Signal Strength
signal_strength (mean (SD))	9.28 (0.68)

Intra-Visit, Normal

	Overall
n	73
Sociodemographic Variables
age (mean (SD))	51.68 (16.15)
Sex = Male (%)	35 (47.9)
Systemic Clinical Variables
Hypertension Diagnosis = Yes (%)	16 (21.9)
Diabetes Mellitus Diagnosis = Yes (%)	3 ( 4.1)
Optic Neuropathy = Yes (%)	1 ( 1.4)
Ophthalmic Clinical Variables
Glaucoma Diagnosis, Binary = Glaucoma (%)	0 ( 0.0)
Glaucoma Diagnosis Laterality, Ordinal (%)
Normal, Bilateral	60 (82.2)
Glaucoma, Bilateral	0 ( 0.0)
Glaucoma, Unilateral	13 (17.8)
Diabetic Retinopathy Diagnosis, Binary = Yes (%)	0 ( 0.0)
Ophthalmic Surgical Variables
Surgical Procedure for Cataract Extraction = Yes (%)	9 (12.3)
Surgical Procedure for Glaucoma (%)
None	67 (91.8)
Laser	6 ( 8.2)
Minimally Invasive Glaucoma Surgery	0 ( 0.0)
Filter	0 ( 0.0)
OCT Angiography Signal Strength
signal_strength (mean (SD))	9.43 (0.60)

Intra-Visit, Glaucoma

	Overall
n	86
Sociodemographic Variables
age (mean (SD))	61.82 (13.84)
Sex = Male (%)	42 ( 48.8)
Systemic Clinical Variables
Hypertension Diagnosis = Yes (%)	29 ( 33.7)
Diabetes Mellitus Diagnosis = Yes (%)	14 ( 16.3)
Optic Neuropathy = Yes (%)	0 ( 0.0)
Ophthalmic Clinical Variables
Glaucoma Diagnosis, Binary = Glaucoma (%)	86 (100.0)
Glaucoma Diagnosis Laterality, Ordinal (%)
Normal, Bilateral	0 ( 0.0)
Glaucoma, Bilateral	71 ( 82.6)
Glaucoma, Unilateral	15 ( 17.4)
Diabetic Retinopathy Diagnosis, Binary = Yes (%)	4 ( 4.7)
Ophthalmic Surgical Variables
Surgical Procedure for Cataract Extraction = Yes (%)	22 ( 25.6)
Surgical Procedure for Glaucoma (%)
None	46 ( 53.5)
Laser	18 ( 20.9)
Minimally Invasive Glaucoma Surgery	2 ( 2.3)
Filter	20 ( 23.3)
OCT Angiography Signal Strength
signal_strength (mean (SD))	9.12 (0.75)

Inter-Visit, Both Eyes OCTA Summary Statistics

Variables in inter-visit dataset

All

Inter-Visit

	Overall
n	148
Sociodemographic Variables
age (mean (SD))	57.19 (15.92)
Sex = Male (%)	71 (48.0)
Systemic Clinical Variables
Hypertension Diagnosis = Yes (%)	43 (29.1)
Diabetes Mellitus Diagnosis = Yes (%)	17 (11.5)
Optic Neuropathy = Yes (%)	1 ( 0.7)
Ophthalmic Clinical Variables
Glaucoma Diagnosis, Binary = Glaucoma (%)	76 (51.4)
Glaucoma Diagnosis Laterality, Ordinal (%)
Normal, Bilateral	59 (39.9)
Glaucoma, Bilateral	71 (48.0)
Glaucoma, Unilateral	18 (12.2)
Diabetic Retinopathy Diagnosis, Binary = Yes (%)	4 ( 2.7)
Ophthalmic Surgical Variables
Surgical Procedure for Cataract Extraction = Yes (%)	28 (18.9)
Surgical Procedure for Glaucoma (%)
None	102 (68.9)
Laser	24 (16.2)
Minimally Invasive Glaucoma Surgery	2 ( 1.4)
Filter	20 (13.5)
OCT Angiography Signal Strength
signal_strength (mean (SD))	9.26 (0.65)

Inter-Visit, Normal

	Overall
n	72
Sociodemographic Variables
age (mean (SD))	52.07 (15.92)
Sex = Male (%)	34 (47.2)
Systemic Clinical Variables
Hypertension Diagnosis = Yes (%)	16 (22.2)
Diabetes Mellitus Diagnosis = Yes (%)	3 ( 4.2)
Optic Neuropathy = Yes (%)	1 ( 1.4)
Ophthalmic Clinical Variables
Glaucoma Diagnosis, Binary = Glaucoma (%)	0 ( 0.0)
Glaucoma Diagnosis Laterality, Ordinal (%)
Normal, Bilateral	59 (81.9)
Glaucoma, Bilateral	0 ( 0.0)
Glaucoma, Unilateral	13 (18.1)
Diabetic Retinopathy Diagnosis, Binary = Yes (%)	0 ( 0.0)
Ophthalmic Surgical Variables
Surgical Procedure for Cataract Extraction = Yes (%)	9 (12.5)
Surgical Procedure for Glaucoma (%)
None	66 (91.7)
Laser	6 ( 8.3)
Minimally Invasive Glaucoma Surgery	0 ( 0.0)
Filter	0 ( 0.0)
OCT Angiography Signal Strength
signal_strength (mean (SD))	9.45 (0.60)

Inter-Visit, Glaucoma

	Overall
n	86
Sociodemographic Variables
age (mean (SD))	61.82 (13.84)
Sex = Male (%)	42 ( 48.8)
Systemic Clinical Variables
Hypertension Diagnosis = Yes (%)	29 ( 33.7)
Diabetes Mellitus Diagnosis = Yes (%)	14 ( 16.3)
Optic Neuropathy = Yes (%)	0 ( 0.0)
Ophthalmic Clinical Variables
Glaucoma Diagnosis, Binary = Glaucoma (%)	86 (100.0)
Glaucoma Diagnosis Laterality, Ordinal (%)
Normal, Bilateral	0 ( 0.0)
Glaucoma, Bilateral	71 ( 82.6)
Glaucoma, Unilateral	15 ( 17.4)
Diabetic Retinopathy Diagnosis, Binary = Yes (%)	4 ( 4.7)
Ophthalmic Surgical Variables
Surgical Procedure for Cataract Extraction = Yes (%)	22 ( 25.6)
Surgical Procedure for Glaucoma (%)
None	46 ( 53.5)
Laser	18 ( 20.9)
Minimally Invasive Glaucoma Surgery	2 ( 2.3)
Filter	20 ( 23.3)
OCT Angiography Signal Strength
signal_strength (mean (SD))	9.08 (0.67)

1 Year

These are the participants we will be using for inter-visit glaucoma

Inter-Visit

	Overall
n	103
Sociodemographic Variables
age (mean (SD))	56.93 (15.64)
Sex = Male (%)	52 (50.5)
Systemic Clinical Variables
Hypertension Diagnosis = Yes (%)	29 (28.2)
Diabetes Mellitus Diagnosis = Yes (%)	14 (13.6)
Optic Neuropathy = Yes (%)	0 ( 0.0)
Ophthalmic Clinical Variables
Glaucoma Diagnosis, Binary = Glaucoma (%)	59 (57.3)
Glaucoma Diagnosis Laterality, Ordinal (%)
Normal, Bilateral	33 (32.0)
Glaucoma, Bilateral	54 (52.4)
Glaucoma, Unilateral	16 (15.5)
Diabetic Retinopathy Diagnosis, Binary = Yes (%)	4 ( 3.9)
Ophthalmic Surgical Variables
Surgical Procedure for Cataract Extraction = Yes (%)	19 (18.4)
Surgical Procedure for Glaucoma (%)
None	70 (68.0)
Laser	14 (13.6)
Minimally Invasive Glaucoma Surgery	1 ( 1.0)
Filter	18 (17.5)
OCT Angiography Signal Strength
signal_strength (mean (SD))	9.20 (0.64)

Inter-Visit, Normal

	Overall
n	44
Sociodemographic Variables
age (mean (SD))	51.17 (14.47)
Sex = Male (%)	20 (45.5)
Systemic Clinical Variables
Hypertension Diagnosis = Yes (%)	7 (15.9)
Diabetes Mellitus Diagnosis = Yes (%)	1 ( 2.3)
Optic Neuropathy = Yes (%)	0 ( 0.0)
Ophthalmic Clinical Variables
Glaucoma Diagnosis, Binary = Glaucoma (%)	0 ( 0.0)
Glaucoma Diagnosis Laterality, Ordinal (%)
Normal, Bilateral	33 (75.0)
Glaucoma, Bilateral	0 ( 0.0)
Glaucoma, Unilateral	11 (25.0)
Diabetic Retinopathy Diagnosis, Binary = Yes (%)	0 ( 0.0)
Ophthalmic Surgical Variables
Surgical Procedure for Cataract Extraction = Yes (%)	5 (11.4)
Surgical Procedure for Glaucoma (%)
None	42 (95.5)
Laser	2 ( 4.5)
Minimally Invasive Glaucoma Surgery	0 ( 0.0)
Filter	0 ( 0.0)
OCT Angiography Signal Strength
signal_strength (mean (SD))	9.45 (0.58)

Inter-Visit, Glaucoma

	Overall
n	67
Sociodemographic Variables
age (mean (SD))	61.16 (14.45)
Sex = Male (%)	35 ( 52.2)
Systemic Clinical Variables
Hypertension Diagnosis = Yes (%)	23 ( 34.3)
Diabetes Mellitus Diagnosis = Yes (%)	13 ( 19.4)
Optic Neuropathy = Yes (%)	0 ( 0.0)
Ophthalmic Clinical Variables
Glaucoma Diagnosis, Binary = Glaucoma (%)	67 (100.0)
Glaucoma Diagnosis Laterality, Ordinal (%)
Normal, Bilateral	0 ( 0.0)
Glaucoma, Bilateral	54 ( 80.6)
Glaucoma, Unilateral	13 ( 19.4)
Diabetic Retinopathy Diagnosis, Binary = Yes (%)	4 ( 6.0)
Ophthalmic Surgical Variables
Surgical Procedure for Cataract Extraction = Yes (%)	16 ( 23.9)
Surgical Procedure for Glaucoma (%)
None	36 ( 53.7)
Laser	12 ( 17.9)
Minimally Invasive Glaucoma Surgery	1 ( 1.5)
Filter	18 ( 26.9)
OCT Angiography Signal Strength
signal_strength (mean (SD))	9.02 (0.64)

6 Months

These are the participants we will be using for inter-visit normal

Inter-Visit

	Overall
n	67
Sociodemographic Variables
age (mean (SD))	57.60 (15.78)
Sex = Male (%)	35 (52.2)
Systemic Clinical Variables
Hypertension Diagnosis = Yes (%)	17 (25.4)
Diabetes Mellitus Diagnosis = Yes (%)	9 (13.4)
Optic Neuropathy = Yes (%)	0 ( 0.0)
Ophthalmic Clinical Variables
Glaucoma Diagnosis, Binary = Glaucoma (%)	44 (65.7)
Glaucoma Diagnosis Laterality, Ordinal (%)
Normal, Bilateral	13 (19.4)
Glaucoma, Bilateral	43 (64.2)
Glaucoma, Unilateral	11 (16.4)
Diabetic Retinopathy Diagnosis, Binary = Yes (%)	3 ( 4.5)
Ophthalmic Surgical Variables
Surgical Procedure for Cataract Extraction = Yes (%)	13 (19.4)
Surgical Procedure for Glaucoma (%)
None	41 (61.2)
Laser	9 (13.4)
Minimally Invasive Glaucoma Surgery	1 ( 1.5)
Filter	16 (23.9)
OCT Angiography Signal Strength
signal_strength (mean (SD))	9.10 (0.65)

Inter-Visit, Normal

Inter-Visit, Glaucoma

	Overall
n	52
Sociodemographic Variables
age (mean (SD))	60.51 (14.74)
Sex = Male (%)	27 ( 51.9)
Systemic Clinical Variables
Hypertension Diagnosis = Yes (%)	16 ( 30.8)
Diabetes Mellitus Diagnosis = Yes (%)	9 ( 17.3)
Optic Neuropathy = Yes (%)	0 ( 0.0)
Ophthalmic Clinical Variables
Glaucoma Diagnosis, Binary = Glaucoma (%)	52 (100.0)
Glaucoma Diagnosis Laterality, Ordinal (%)
Normal, Bilateral	0 ( 0.0)
Glaucoma, Bilateral	43 ( 82.7)
Glaucoma, Unilateral	9 ( 17.3)
Diabetic Retinopathy Diagnosis, Binary = Yes (%)	3 ( 5.8)
Ophthalmic Surgical Variables
Surgical Procedure for Cataract Extraction = Yes (%)	13 ( 25.0)
Surgical Procedure for Glaucoma (%)
None	27 ( 51.9)
Laser	8 ( 15.4)
Minimally Invasive Glaucoma Surgery	1 ( 1.9)
Filter	16 ( 30.8)
OCT Angiography Signal Strength
signal_strength (mean (SD))	8.98 (0.64)

Exploratory Data Analysis

Scatter Plots

Scatter plots of OCTA variables by Subject ID for about 10 individuals randomly sampled. These are separated by intra- and inter-visit data sets, and are useful for understanding the data better.

Vessel Area Density

Vessel Area Density, Zeiss

Vessel Diameter

Vessel Skeleton Density

Vessel Perimeter Index

Vessel Complexity Index

Flow Impairment Zone

Flux

Flux, Zeiss

Spaghetti Plots

Spaghetti plots of OCTA variables for about 10 individuals randomly sampled.

Vessel Area Density

Vessel Area Density, Zeiss

Vessel Diameter

Vessel Skeleton Density

Vessel Perimeter Index

Vessel Complexity Index

Flow Impairment Zone

Flux

Flux, Zeiss

Bland-Altman Plots

Coding of Bland-Altman (BA) plots is explained in this blog post.

Intra-Visit Bland-Altman Plots

Intra-Visit Bland-Altman Plots of OCTA Variables

Vessel Area Density

Vessel Area Density, Zeiss

Vessel Diameter

Vessel Skeleton Density

Vessel Perimeter Index

Vessel Complexity Index

Flow Impairment Zone

Flux

Flux, Zeiss

Outliers

Assess some of the observations outside of expected limits.

eyeid	ptid	signal_strength	female	eye_imaged	image_area	image_size	image_method	exam_date	time_stamp	v_diameter	v_area_density	v_skeleton_density	v_perimeter_index	v_complexity_index	flow_impair_zone	flux	zeiss_v_area_density	zeiss_flux	age	htn_dx	dm_dx	nro_dx	dr_dx	glc_sus_dx	glc_dx	surg_proc_glaucoma	surg_proc_catextract	glc_dx_bin	dr_dx_bin	glc_dx_bin_people	n_msr_day	order_obs
11	1226815	9	Female	Left	ONH	6x6	Angiography	2019-10-25	2019-10-25 12:41:03	30.29640	0.1370255	0.04522833	0.1273263	2149.126	19.5292	0.04483744	0.357	0.255	74.0	No	No	No	None	None	Severe	Laser	No	Glaucoma	No	Glaucoma, Bilateral	2	1
11	1226815	9	Female	Left	ONH	6x6	Angiography	2019-10-25	2019-10-25 12:42:40	28.69309	0.1573387	0.05483507	0.1448204	2425.982	17.3898	0.05181468	0.358	0.262	74.0	No	No	No	None	None	Severe	Laser	No	Glaucoma	No	Glaucoma, Bilateral	2	2
18	1380225	10	Female	Left	ONH	6x6	Angiography	2019-03-20	2019-03-20 11:25:51	25.34368	0.2927191	0.11549981	0.2730479	4419.194	5.8646	0.09498110	0.391	0.312	59.5	No	No	No	None	Severe	None	None	No	Normal	No	Normal, Bilateral	3	1
18	1380225	10	Female	Left	ONH	6x6	Angiography	2019-03-20	2019-03-20 11:26:24	25.93677	0.2808006	0.10826349	0.2626908	4354.005	6.0290	0.09104601	0.387	0.308	59.5	No	No	No	None	Severe	None	None	No	Normal	No	Normal, Bilateral	3	2
18	1380225	10	Female	Left	ONH	6x6	Angiography	2019-03-20	2019-03-20 11:26:54	25.57051	0.2913801	0.11395163	0.2715677	4492.345	6.0963	0.09378992	0.391	0.314	59.5	No	No	No	None	Severe	None	None	No	Normal	No	Normal, Bilateral	3	3
21	138721	8	Female	Right	ONH	6x6	Angiography	2018-03-23	2018-03-23 12:35:54	24.11877	0.3366931	0.13959797	0.3099195	4770.301	6.6043	0.12174832	0.415	0.354	71.0	No	No	No	None	None	Severe	None	No	Glaucoma	No	Glaucoma, Unilateral	3	1
21	138721	9	Female	Right	ONH	6x6	Angiography	2018-03-23	2018-03-23 12:36:56	24.79561	0.3413820	0.13767841	0.3139906	5034.907	6.1268	0.12247720	0.407	0.358	71.0	No	No	No	None	None	Severe	None	No	Glaucoma	No	Glaucoma, Unilateral	3	2
21	138721	7	Female	Right	ONH	6x6	Angiography	2018-03-23	2018-03-23 12:44:53	24.65734	0.3008142	0.12199783	0.2776850	4386.743	7.7867	0.10278178	0.398	0.331	71.0	No	No	No	None	None	Severe	None	No	Glaucoma	No	Glaucoma, Unilateral	3	3
39	1722883	10	Male	Right	ONH	6x6	Angiography	2019-08-09	2019-08-09 10:34:25	25.54585	0.3697135	0.14472546	0.3375627	5470.442	4.0666	0.13764308	0.403	0.371	62.8	No	No	No	None	Severe	None	None	No	Normal	No	Normal, Bilateral	3	1
39	1722883	10	Male	Right	ONH	6x6	Angiography	2019-08-09	2019-08-09 10:35:07	25.24136	0.3861241	0.15297278	0.3529328	5781.427	3.6101	0.13843919	0.408	0.375	62.8	No	No	No	None	Severe	None	None	No	Normal	No	Normal, Bilateral	3	2
39	1722883	10	Male	Right	ONH	6x6	Angiography	2019-08-09	2019-08-09 10:35:44	24.32060	0.4155198	0.17085094	0.3791646	6189.701	2.6544	0.15392797	0.427	0.389	62.8	No	No	No	None	Severe	None	None	No	Normal	No	Normal, Bilateral	3	3
40	1755703	9	Female	Left	ONH	6x6	Angiography	2019-01-23	2019-01-23 08:58:07	25.44699	0.3225155	0.12674015	0.2954372	4904.017	7.0431	0.11022962	0.423	0.343	60.0	No	No	No	None	Severe	None	None	No	Normal	No	Normal, Bilateral	2	1
40	1755703	9	Female	Left	ONH	6x6	Angiography	2019-01-23	2019-01-23 08:58:33	25.48799	0.2949723	0.11572993	0.2713770	4545.290	9.9067	0.10021295	0.422	0.329	60.0	No	No	No	None	Severe	None	None	No	Normal	No	Normal, Bilateral	2	2
58	2083485	8	Male	Right	ONH	6x6	Angiography	2019-06-05	2019-06-05 11:04:06	26.75168	0.2667196	0.09970197	0.2453661	3983.900	10.8190	0.09260453	0.381	0.323	68.0	Yes	No	No	None	Moderate	None	None	Yes	Normal	No	Normal, Bilateral	3	1
58	2083485	8	Male	Right	ONH	6x6	Angiography	2019-06-05	2019-06-05 11:04:42	26.42129	0.2593079	0.09814356	0.2388267	3917.684	10.5598	0.09140341	0.387	0.319	68.0	Yes	No	No	None	Moderate	None	None	Yes	Normal	No	Normal, Bilateral	3	2
58	2083485	8	Male	Right	ONH	6x6	Angiography	2019-06-05	2019-06-05 11:05:32	27.14406	0.2323210	0.08558813	0.2144602	3489.403	11.8333	0.08029139	0.368	0.310	68.0	Yes	No	No	None	Moderate	None	None	Yes	Normal	No	Normal, Bilateral	3	3
92	51313	10	Female	Right	ONH	6x6	Angiography	2019-10-04	2019-10-04 13:46:37	25.37820	0.2431212	0.09579924	0.2268217	3792.671	9.7405	0.07838918	0.377	0.296	65.4	No	No	No	None	None	Severe	None	No	Glaucoma	No	Glaucoma, Unilateral	2	1
92	51313	9	Female	Right	ONH	6x6	Angiography	2019-10-04	2019-10-04 13:49:13	25.35997	0.2507987	0.09889549	0.2331802	3850.294	9.1813	0.08112071	0.387	0.297	65.4	No	No	No	None	None	Severe	None	No	Glaucoma	No	Glaucoma, Unilateral	2	2
95	56867	10	Male	Right	ONH	6x6	Angiography	2019-09-06	2019-09-06 13:47:30	24.95075	0.3282209	0.13154753	0.3035419	5033.684	7.0176	0.11306028	0.413	0.339	83.0	Yes	No	No	None	Moderate	None	Laser	Yes	Normal	No	Normal, Bilateral	3	1
95	56867	10	Male	Right	ONH	6x6	Angiography	2019-09-06	2019-09-06 13:47:51	25.19313	0.3170639	0.12585328	0.2917371	4815.958	7.0559	0.11002868	0.412	0.338	83.0	Yes	No	No	None	Moderate	None	Laser	Yes	Normal	No	Normal, Bilateral	3	2
95	56867	10	Male	Right	ONH	6x6	Angiography	2019-09-06	2019-09-06 13:48:13	25.30722	0.3020664	0.11935978	0.2789155	4672.353	8.1056	0.10262727	0.409	0.329	83.0	Yes	No	No	None	Moderate	None	Laser	Yes	Normal	No	Normal, Bilateral	3	3
130	7005925	9	Female	Left	ONH	6x6	Angiography	2018-08-02	2018-08-02 09:15:19	26.99969	0.2754437	0.10201736	0.2530386	4119.877	9.5881	0.09242421	0.414	0.310	58.0	Yes	No	No	None	None	Moderate	Laser	No	Glaucoma	No	Glaucoma, Bilateral	2	1
130	7005925	10	Female	Left	ONH	6x6	Angiography	2018-08-02	2018-08-02 09:15:53	26.30913	0.2907589	0.11051634	0.2666798	4356.173	8.7396	0.09770604	0.416	0.315	58.0	Yes	No	No	None	None	Moderate	Laser	No	Glaucoma	No	Glaucoma, Bilateral	2	2
143	7131431	9	Male	Left	ONH	6x6	Angiography	2018-08-15	2018-08-15 09:41:56	24.21184	0.4091970	0.16900697	0.3747174	5942.869	1.4010	0.14646586	0.454	0.365	51.0	No	No	No	None	Mild	None	None	No	Normal	No	Normal, Bilateral	2	1
143	7131431	10	Male	Left	ONH	6x6	Angiography	2018-08-15	2018-08-15 09:43:08	24.20815	0.4025210	0.16627498	0.3689489	5702.549	1.8829	0.14140949	0.454	0.350	51.0	No	No	No	None	Mild	None	None	No	Normal	No	Normal, Bilateral	2	2
171	7258827	10	Female	Left	ONH	6x6	Angiography	2018-12-12	2018-12-12 10:06:49	24.84787	0.4359879	0.17546287	0.3953800	6290.749	2.3042	0.17096520	0.441	0.414	20.0	Yes	No	No	None	None	Mild	Filter	No	Glaucoma	No	Glaucoma, Bilateral	3	1
171	7258827	10	Female	Left	ONH	6x6	Angiography	2018-12-12	2018-12-12 10:07:14	24.99868	0.4291201	0.17165714	0.3905509	6230.003	2.6333	0.16776221	0.438	0.411	20.0	Yes	No	No	None	None	Mild	Filter	No	Glaucoma	No	Glaucoma, Bilateral	3	2
171	7258827	10	Female	Left	ONH	6x6	Angiography	2018-12-12	2018-12-12 10:07:36	24.88477	0.4121186	0.16561075	0.3765523	6076.072	3.5818	0.15629089	0.433	0.397	20.0	Yes	No	No	None	None	Mild	Filter	No	Glaucoma	No	Glaucoma, Bilateral	3	3
174	725907	8	Male	Right	ONH	6x6	Angiography	2019-02-27	2019-02-27 09:00:30	29.25085	0.1624065	0.05552199	0.1487154	2475.067	14.2008	0.05396190	0.360	0.272	46.0	No	No	No	None	None	Severe	Laser	No	Glaucoma	No	Glaucoma, Bilateral	3	1
174	725907	8	Male	Right	ONH	6x6	Angiography	2019-02-27	2019-02-27 09:00:54	28.14171	0.1786021	0.06346527	0.1635242	2731.644	12.8631	0.05996023	0.358	0.281	46.0	No	No	No	None	None	Severe	Laser	No	Glaucoma	No	Glaucoma, Bilateral	3	2
174	725907	9	Male	Right	ONH	6x6	Angiography	2019-02-27	2019-02-27 09:01:18	27.58670	0.2007703	0.07277793	0.1839710	3072.000	10.9801	0.06768001	0.356	0.293	46.0	No	No	No	None	None	Severe	Laser	No	Glaucoma	No	Glaucoma, Bilateral	3	3
183	7281737	9	Female	Left	ONH	6x6	Angiography	2019-02-08	2019-02-08 09:40:28	25.93341	0.2528107	0.09748458	0.2353340	3984.935	8.3944	0.08184594	0.380	0.301	72.3	No	No	No	None	None	Moderate	None	Yes	Glaucoma	No	Glaucoma, Unilateral	3	1
183	7281737	8	Female	Left	ONH	6x6	Angiography	2019-02-08	2019-02-08 09:40:59	26.26110	0.2393146	0.09112893	0.2231295	3744.725	9.8493	0.07699201	0.371	0.298	72.3	No	No	No	None	None	Moderate	None	Yes	Glaucoma	No	Glaucoma, Unilateral	3	2
183	7281737	9	Female	Left	ONH	6x6	Angiography	2019-02-08	2019-02-08 09:41:30	25.07638	0.3100368	0.12363701	0.2864197	4771.679	5.3852	0.10217958	0.403	0.320	72.3	No	No	No	None	None	Moderate	None	Yes	Glaucoma	No	Glaucoma, Unilateral	3	3
192	7349639	9	Female	Right	ONH	6x6	Angiography	2018-05-17	2018-05-17 07:12:52	27.55197	0.1913157	0.06943811	0.1778472	2944.142	14.1081	0.06679617	0.350	0.285	78.0	Yes	No	No	None	None	Severe	Filter	Yes	Glaucoma	No	Glaucoma, Bilateral	2	1
192	7349639	10	Female	Right	ONH	6x6	Angiography	2018-05-17	2018-05-17 07:13:22	28.78626	0.1813382	0.06299471	0.1685112	2775.510	15.2113	0.06136395	0.346	0.281	78.0	Yes	No	No	None	None	Severe	Filter	Yes	Glaucoma	No	Glaucoma, Bilateral	2	2
208	7519765	8	Male	Left	ONH	6x6	Angiography	2019-08-30	2019-08-30 15:30:14	27.20185	0.2107805	0.07748754	0.1948209	3237.692	12.4292	0.06973939	0.367	0.295	61.0	Yes	No	No	None	None	Severe	Laser	Yes	Glaucoma	No	Glaucoma, Bilateral	2	1
208	7519765	10	Male	Left	ONH	6x6	Angiography	2019-08-30	2019-08-30 15:32:55	25.39811	0.2800877	0.11027896	0.2571687	4292.763	8.2164	0.09770912	0.379	0.328	61.0	Yes	No	No	None	None	Severe	Laser	Yes	Glaucoma	No	Glaucoma, Bilateral	2	2
220	7618939	9	Male	Right	ONH	6x6	Angiography	2019-11-01	2019-11-01 10:00:51	24.31144	0.3621905	0.14897947	0.3345446	5352.807	2.8209	0.12682591	0.425	0.358	63.9	No	No	No	None	Mild	None	None	Yes	Normal	No	Glaucoma, Unilateral	2	1
220	7618939	9	Male	Right	ONH	6x6	Angiography	2019-11-01	2019-11-01 10:01:46	23.92392	0.3362092	0.14053265	0.3104898	5173.177	4.9099	0.11296480	0.416	0.344	63.9	No	No	No	None	Mild	None	None	Yes	Normal	No	Glaucoma, Unilateral	2	2
232	7685911	10	Male	Left	ONH	6x6	Angiography	2019-05-17	2019-05-17 09:36:40	24.43870	0.4260757	0.17434466	0.3894777	6321.509	1.9411	0.15991722	0.456	0.377	41.9	No	No	No	None	Mild	None	None	No	Normal	No	Normal, Bilateral	3	1
232	7685911	10	Male	Left	ONH	6x6	Angiography	2019-05-17	2019-05-17 09:37:09	24.15303	0.4292999	0.17774163	0.3924835	6372.214	1.6997	0.16470424	0.453	0.386	41.9	No	No	No	None	Mild	None	None	No	Normal	No	Normal, Bilateral	3	2
232	7685911	10	Male	Left	ONH	6x6	Angiography	2019-05-17	2019-05-17 09:37:41	24.34898	0.4349116	0.17861592	0.3974844	6497.414	1.3569	0.16220947	0.462	0.379	41.9	No	No	No	None	Mild	None	None	No	Normal	No	Normal, Bilateral	3	3

Inter-Visit Bland-Altman Plots

Inter-Visit Bland-Altman Plots of OCTA Variables

Vessel Area Density

Vessel Area Density, Zeiss

Vessel Diameter

Vessel Skeleton Density

Vessel Perimeter Index

Vessel Complexity Index

Flow Impairment Zone

Flux

Flux, Zeiss

Outliers

Assess some of the observations outside of expected limits.

eyeid	ptid	signal_strength	female	eye_imaged	image_area	image_size	image_method	exam_date	time_stamp	v_diameter	v_area_density	v_skeleton_density	v_perimeter_index	v_complexity_index	flow_impair_zone	flux	zeiss_v_area_density	zeiss_flux	age	htn_dx	dm_dx	nro_dx	dr_dx	glc_sus_dx	glc_dx	surg_proc_glaucoma	surg_proc_catextract	glc_dx_bin	dr_dx_bin	glc_dx_bin_people	order_obs	day_one	diff_date	ind_n_day	n_exams
42	1787031	8	Female	Right	ONH	6x6	Angiography	2018-10-10	2018-10-10 10:45:55	25.09862	0.2859831	0.11394375	0.2634102	4329.615	10.3229	0.09907050	0.380	0.288	52.0	No	No	No	None	Severe	None	None	Yes	Normal	No	Normal, Bilateral	1	2018-10-10	0 days	1	3
42	1787031	9	Female	Right	ONH	6x6	Angiography	2019-04-10	2019-04-10 11:47:25	25.44504	0.2934491	0.11532663	0.2682686	4272.115	9.0475	0.10338978	0.386	0.286	52.0	No	No	No	None	Severe	None	None	Yes	Normal	No	Normal, Bilateral	2	2018-10-10	182 days	1	3
42	1787031	7	Female	Right	ONH	6x6	Angiography	2019-05-08	2019-05-08 11:09:31	25.08622	0.3086875	0.12305063	0.2841450	4433.711	7.5607	0.10895244	0.380	0.278	52.0	No	No	No	None	Severe	None	None	Yes	Normal	No	Normal, Bilateral	3	2018-10-10	210 days	1	3
75	2360743	10	Male	Left	ONH	6x6	Angiography	2018-08-27	2018-08-27 16:11:17	27.78426	0.1930609	0.06948571	0.1805683	2985.314	13.0653	0.06529053	0.291	0.306	63.0	No	No	No	None	None	Moderate	None	No	Glaucoma	No	Glaucoma, Bilateral	1	2018-08-27	0 days	1	6
75	2360743	10	Male	Left	ONH	6x6	Angiography	2019-03-04	2019-03-04 17:12:06	27.87001	0.2087222	0.07489131	0.1947559	3226.429	12.4484	0.06990845	0.302	0.308	63.0	No	No	No	None	None	Moderate	None	No	Glaucoma	No	Glaucoma, Bilateral	2	2018-08-27	189 days	1	6
75	2360743	9	Male	Left	ONH	6x6	Angiography	2019-07-19	2019-07-19 11:00:41	27.48735	0.1704014	0.06199265	0.1601514	2673.694	14.4143	0.05653714	0.297	0.292	63.0	No	No	No	None	None	Moderate	None	No	Glaucoma	No	Glaucoma, Bilateral	3	2018-08-27	326 days	1	6
75	2360743	9	Male	Left	ONH	6x6	Angiography	2019-09-13	2019-09-13 10:16:26	27.08991	0.1727003	0.06375077	0.1614856	2649.738	13.0485	0.05749367	0.293	0.289	63.0	No	No	No	None	None	Moderate	None	No	Glaucoma	No	Glaucoma, Bilateral	4	2018-08-27	382 days	1	6
75	2360743	10	Male	Left	ONH	6x6	Angiography	2019-10-18	2019-10-18 10:00:02	27.46399	0.1728102	0.06292248	0.1616125	2693.818	13.8972	0.05646246	0.304	0.288	63.0	No	No	No	None	None	Moderate	None	No	Glaucoma	No	Glaucoma, Bilateral	5	2018-08-27	417 days	1	6
75	2360743	9	Male	Left	ONH	6x6	Angiography	2019-11-22	2019-11-22 09:52:43	27.16595	0.1915620	0.07051549	0.1791181	2946.412	12.7424	0.06469231	0.299	0.299	63.0	No	No	No	None	None	Moderate	None	No	Glaucoma	No	Glaucoma, Bilateral	6	2018-08-27	452 days	1	6
82	35357	10	Female	Left	ONH	6x6	Angiography	2017-03-16	2017-03-16 15:01:12	24.82872	0.3273775	0.13185434	0.3045946	4978.047	7.0865	0.11088273	0.438	0.331	80.0	No	No	No	None	None	Mild	None	Yes	Glaucoma	No	Glaucoma, Bilateral	1	2017-03-16	0 days	1	2
82	35357	10	Female	Left	ONH	6x6	Angiography	2019-11-06	2019-11-06 09:13:11	24.08127	0.3504950	0.14554675	0.3246427	5449.887	5.5967	0.11861236	0.446	0.338	80.0	No	No	No	None	None	Mild	None	Yes	Glaucoma	No	Glaucoma, Bilateral	2	2017-03-16	965 days	1	2
92	51313	8	Female	Right	ONH	6x6	Angiography	2019-05-03	2019-05-03 14:18:00	27.45707	0.1756779	0.06398276	0.1636341	2803.662	15.9611	0.05454180	0.393	0.262	65.4	No	No	No	None	None	Severe	None	No	Glaucoma	No	Glaucoma, Unilateral	1	2019-05-03	0 days	1	2
92	51313	10	Female	Right	ONH	6x6	Angiography	2019-10-04	2019-10-04 13:46:37	25.37820	0.2431212	0.09579924	0.2268217	3792.671	9.7405	0.07838918	0.377	0.296	65.4	No	No	No	None	None	Severe	None	No	Glaucoma	No	Glaucoma, Unilateral	2	2019-05-03	154 days	1	2
220	7618939	8	Male	Right	ONH	6x6	Angiography	2019-09-27	2019-09-27 09:31:48	24.61454	0.3086070	0.12537588	0.2857071	4605.931	6.5831	0.10433904	0.421	0.330	63.9	No	No	No	None	Mild	None	None	Yes	Normal	No	Glaucoma, Unilateral	1	2019-09-27	0 days	1	2
220	7618939	9	Male	Right	ONH	6x6	Angiography	2019-11-01	2019-11-01 10:00:51	24.31144	0.3621905	0.14897947	0.3345446	5352.807	2.8209	0.12682591	0.425	0.358	63.9	No	No	No	None	Mild	None	None	Yes	Normal	No	Glaucoma, Unilateral	2	2019-09-27	35 days	1	2
232	7685911	10	Male	Left	ONH	6x6	Angiography	2019-05-17	2019-05-17 09:36:40	24.43870	0.4260757	0.17434466	0.3894777	6321.509	1.9411	0.15991722	0.456	0.377	41.9	No	No	No	None	Mild	None	None	No	Normal	No	Normal, Bilateral	1	2019-05-17	0 days	1	2
232	7685911	7	Male	Left	ONH	6x6	Angiography	2019-10-25	2019-10-25 09:03:28	24.78055	0.3231436	0.13040208	0.2996570	4879.827	7.5546	0.11223840	0.438	0.328	41.9	No	No	No	None	Mild	None	None	No	Normal	No	Normal, Bilateral	2	2019-05-17	161 days	1	2

Reliability, One Eye

Reliability of OCTA Variables

Calculate the within-subject standard deviation \((S_w)\), the within-subject coefficient of repeatability \((CR_w)\), and the within-subject coefficient of variation \((CV_w)\) for a given measurement variable \(x\).

Table 2: Reliability

Table 2 shows Reliability estimates of vessel density measurements.

This table was modeled after Table 2 in Venugopal (2018).²

Intra-Visit Repeatability

Normal

OCTA Variable	n_measure	µ	Sw	Sw 95% CL	CRw	CRw 95% CL	CVw	CVw 95% CL
Vessel Diameter (units?)	180	24.921	0.240	(0.228, 0.253)	0.665	(0.631, 0.700)	0.963	(0.913, 1.013)
Vessel Area Density	180	0.362	0.014	(0.014, 0.014)	0.038	(0.038, 0.039)	3.832	(3.820, 3.843)
Vessel Area Density, Zeiss	180	0.429	0.006	(0.006, 0.006)	0.016	(0.016, 0.016)	1.369	(1.368, 1.371)
Vessel Skeleton Density (units?)	180	0.146	0.006	(0.006, 0.006)	0.017	(0.017, 0.017)	4.215	(4.210, 4.221)
Vessel Perimeter Index (units?)	180	0.331	0.012	(0.012, 0.012)	0.034	(0.034, 0.034)	3.699	(3.689, 3.709)
Vessel Complexity Index (units?)	180	5379.302	200.808	(-7047.568, 7449.184)	556.611	(-19534.863, 20648.084)	3.733	(-131.013, 138.479)
Flow Impairment Zone (units?)	180	5.037	0.832	(0.615, 1.050)	2.307	(1.704, 2.910)	16.524	(12.203, 20.844)
Flux	180	0.130	0.006	(0.006, 0.006)	0.017	(0.017, 0.017)	4.673	(4.668, 4.679)
Flux, Zeiss	180	0.360	0.007	(0.007, 0.007)	0.018	(0.018, 0.018)	1.847	(1.844, 1.849)

Glaucoma

OCTA Variable	n_measure	µ	Sw	Sw 95% CL	CRw	CRw 95% CL	CVw	CVw 95% CL
Vessel Diameter (units?)	202	26.249	0.409	(0.368, 0.449)	1.133	(1.020, 1.246)	1.557	(1.402, 1.712)
Vessel Area Density	202	0.278	0.024	(0.024, 0.025)	0.068	(0.067, 0.068)	8.783	(8.684, 8.883)
Vessel Area Density, Zeiss	202	0.397	0.007	(0.007, 0.007)	0.019	(0.019, 0.019)	1.767	(1.765, 1.770)
Vessel Skeleton Density (units?)	202	0.108	0.011	(0.011, 0.011)	0.030	(0.029, 0.030)	9.857	(9.809, 9.904)
Vessel Perimeter Index (units?)	202	0.256	0.022	(0.022, 0.022)	0.061	(0.061, 0.062)	8.657	(8.568, 8.746)
Vessel Complexity Index (units?)	202	4213.362	360.577	(-59387.279, 60108.434)	999.470	(-164613.140, 166612.079)	8.558	(-1409.499, 1426.614)
Flow Impairment Zone (units?)	202	9.250	1.462	(0.777, 2.148)	4.053	(2.153, 5.953)	15.806	(8.396, 23.216)
Flux	202	0.096	0.010	(0.010, 0.010)	0.027	(0.027, 0.027)	10.108	(10.060, 10.156)
Flux, Zeiss	202	0.320	0.007	(0.007, 0.007)	0.019	(0.019, 0.019)	2.119	(2.116, 2.122)

Inter-Visit Reproducibility

Restrict to repeat measurements within a given window of time to minimize differences due to real changes in psychopathology.

Inter-Visit Reproducibility Normal

Normal, All

OCTA Variable	n_measure	µ	Sw	Sw 95% CL	CRw	CRw 95% CL	CVw	CVw 95% CL
Vessel Diameter (units?)	151	24.877	0.341	(0.317, 0.365)	0.946	(0.880, 1.012)	1.372	(1.276, 1.468)
Vessel Area Density	151	0.361	0.024	(0.024, 0.024)	0.067	(0.067, 0.068)	6.724	(6.681, 6.767)
Vessel Area Density, Zeiss	151	0.430	0.009	(0.009, 0.009)	0.026	(0.026, 0.026)	2.166	(2.162, 2.170)
Vessel Skeleton Density (units?)	151	0.146	0.011	(0.011, 0.011)	0.029	(0.029, 0.030)	7.289	(7.269, 7.308)
Vessel Perimeter Index (units?)	151	0.331	0.021	(0.021, 0.021)	0.058	(0.058, 0.058)	6.307	(6.272, 6.342)
Vessel Complexity Index (units?)	151	5357.350	333.268	(-30444.472, 31111.007)	923.771	(-84387.771, 86235.313)	6.221	(-568.275, 580.716)
Flow Impairment Zone (units?)	151	5.136	1.410	(0.884, 1.936)	3.909	(2.451, 5.367)	27.460	(17.217, 37.703)
Flux	151	0.129	0.011	(0.011, 0.011)	0.031	(0.031, 0.031)	8.697	(8.671, 8.722)
Flux, Zeiss	151	0.358	0.012	(0.012, 0.012)	0.032	(0.032, 0.032)	3.259	(3.250, 3.269)

Normal, 365 Days

OCTA Variable	n_measure	µ	Sw	Sw 95% CL	CRw	CRw 95% CL	CVw	CVw 95% CL
Vessel Diameter (units?)	85	24.852	0.371	(0.329, 0.412)	1.027	(0.911, 1.143)	1.491	(1.322, 1.660)
Vessel Area Density	85	0.361	0.022	(0.022, 0.022)	0.062	(0.061, 0.062)	6.155	(6.102, 6.208)
Vessel Area Density, Zeiss	85	0.428	0.008	(0.008, 0.008)	0.023	(0.023, 0.023)	1.961	(1.957, 1.966)
Vessel Skeleton Density (units?)	85	0.146	0.010	(0.010, 0.010)	0.028	(0.028, 0.028)	6.871	(6.846, 6.895)
Vessel Perimeter Index (units?)	85	0.331	0.020	(0.020, 0.020)	0.055	(0.055, 0.056)	6.016	(5.971, 6.061)
Vessel Complexity Index (units?)	85	5337.511	311.185	(-37255.264, 37877.634)	862.561	(-103266.323, 104991.445)	5.830	(-697.989, 709.650)
Flow Impairment Zone (units?)	85	5.070	1.357	(0.683, 2.030)	3.760	(1.894, 5.626)	26.758	(13.478, 40.038)
Flux	85	0.129	0.010	(0.010, 0.010)	0.027	(0.027, 0.027)	7.568	(7.537, 7.598)
Flux, Zeiss	85	0.358	0.010	(0.010, 0.010)	0.029	(0.029, 0.029)	2.900	(2.888, 2.912)

Normal, 180 Days

OCTA Variable	n_measure	µ	Sw	Sw 95% CL	CRw	CRw 95% CL	CVw	CVw 95% CL
Vessel Diameter (units?)	42	24.699	0.407	(0.342, 0.471)	1.127	(0.948, 1.306)	1.647	(1.385, 1.908)
Vessel Area Density	42	0.365	0.029	(0.028, 0.029)	0.079	(0.078, 0.080)	7.822	(7.725, 7.918)
Vessel Area Density, Zeiss	42	0.431	0.009	(0.009, 0.009)	0.024	(0.024, 0.024)	2.040	(2.034, 2.046)
Vessel Skeleton Density (units?)	42	0.148	0.013	(0.013, 0.013)	0.036	(0.035, 0.036)	8.690	(8.647, 8.734)
Vessel Perimeter Index (units?)	42	0.335	0.026	(0.025, 0.026)	0.071	(0.070, 0.072)	7.627	(7.545, 7.708)
Vessel Complexity Index (units?)	42	5436.781	390.390	(-69753.718, 70534.497)	1082.105	(-193347.441, 195511.651)	7.181	(-1282.997, 1297.358)
Flow Impairment Zone (units?)	42	4.602	1.665	(0.418, 2.911)	4.614	(1.159, 8.070)	36.175	(9.084, 63.267)
Flux	42	0.130	0.013	(0.013, 0.013)	0.035	(0.035, 0.035)	9.809	(9.752, 9.866)
Flux, Zeiss	42	0.357	0.014	(0.013, 0.014)	0.038	(0.037, 0.038)	3.790	(3.767, 3.812)

Inter-Visit Reproducibility Glaucoma

Glaucoma, All

OCTA Variable	n_measure	µ	Sw	Sw 95% CL	CRw	CRw 95% CL	CVw	CVw 95% CL
Vessel Diameter (units?)	225	26.456	0.596	(0.532, 0.660)	1.652	(1.475, 1.829)	2.253	(2.012, 2.495)
Vessel Area Density	225	0.268	0.031	(0.031, 0.032)	0.087	(0.086, 0.087)	11.674	(11.569, 11.779)
Vessel Area Density, Zeiss	225	0.392	0.009	(0.009, 0.009)	0.024	(0.024, 0.024)	2.192	(2.189, 2.194)
Vessel Skeleton Density (units?)	225	0.104	0.014	(0.013, 0.014)	0.037	(0.037, 0.038)	13.047	(12.998, 13.097)
Vessel Perimeter Index (units?)	225	0.246	0.028	(0.028, 0.029)	0.079	(0.078, 0.079)	11.535	(11.442, 11.629)
Vessel Complexity Index (units?)	225	4056.458	451.493	(-56816.268, 57719.254)	1251.474	(-157486.660, 159989.608)	11.130	(-1400.637, 1422.898)
Flow Impairment Zone (units?)	225	9.695	1.976	(1.205, 2.747)	5.476	(3.339, 7.613)	20.378	(12.426, 28.330)
Flux	225	0.093	0.013	(0.013, 0.013)	0.036	(0.036, 0.036)	14.001	(13.947, 14.055)
Flux, Zeiss	225	0.317	0.012	(0.012, 0.012)	0.032	(0.032, 0.032)	3.645	(3.639, 3.651)

Glaucoma, 365 Days

OCTA Variable	n_measure	µ	Sw	Sw 95% CL	CRw	CRw 95% CL	CVw	CVw 95% CL
Vessel Diameter (units?)	161	26.627	0.620	(0.546, 0.694)	1.719	(1.514, 1.923)	2.329	(2.051, 2.606)
Vessel Area Density	161	0.260	0.032	(0.032, 0.032)	0.089	(0.088, 0.090)	12.291	(12.155, 12.426)
Vessel Area Density, Zeiss	161	0.390	0.009	(0.009, 0.009)	0.025	(0.025, 0.025)	2.315	(2.312, 2.319)
Vessel Skeleton Density (units?)	161	0.100	0.014	(0.014, 0.014)	0.038	(0.038, 0.038)	13.783	(13.718, 13.848)
Vessel Perimeter Index (units?)	161	0.239	0.029	(0.029, 0.029)	0.081	(0.080, 0.082)	12.169	(12.047, 12.291)
Vessel Complexity Index (units?)	161	3939.684	461.849	(-72837.153, 73760.852)	1280.181	(-201894.289, 204454.651)	11.723	(-1848.807, 1872.253)
Flow Impairment Zone (units?)	161	10.117	2.037	(1.076, 2.998)	5.646	(2.982, 8.311)	20.135	(10.634, 29.636)
Flux	161	0.090	0.013	(0.013, 0.013)	0.036	(0.036, 0.037)	14.641	(14.571, 14.710)
Flux, Zeiss	161	0.314	0.011	(0.011, 0.011)	0.031	(0.031, 0.031)	3.586	(3.579, 3.593)

Glaucoma, 180 Days

OCTA Variable	n_measure	µ	Sw	Sw 95% CL	CRw	CRw 95% CL	CVw	CVw 95% CL
Vessel Diameter (units?)	115	26.862	0.647	(0.546, 0.747)	1.792	(1.515, 2.070)	2.407	(2.034, 2.780)
Vessel Area Density	115	0.255	0.032	(0.031, 0.032)	0.088	(0.086, 0.089)	12.398	(12.233, 12.563)
Vessel Area Density, Zeiss	115	0.389	0.010	(0.010, 0.010)	0.027	(0.027, 0.027)	2.473	(2.468, 2.477)
Vessel Skeleton Density (units?)	115	0.098	0.014	(0.014, 0.014)	0.038	(0.037, 0.038)	13.927	(13.848, 14.006)
Vessel Perimeter Index (units?)	115	0.235	0.029	(0.029, 0.029)	0.080	(0.079, 0.081)	12.312	(12.163, 12.462)
Vessel Complexity Index (units?)	115	3855.582	460.356	(-91384.759, 92305.471)	1276.041	(-253305.629, 255857.711)	11.940	(-2370.194, 2394.074)
Flow Impairment Zone (units?)	115	10.446	2.149	(0.887, 3.410)	5.956	(2.459, 9.453)	20.570	(8.492, 32.647)
Flux	115	0.089	0.013	(0.013, 0.013)	0.036	(0.036, 0.036)	14.718	(14.634, 14.802)
Flux, Zeiss	115	0.311	0.011	(0.011, 0.011)	0.031	(0.031, 0.031)	3.605	(3.597, 3.614)

Calculating Reliability Statistics

Explanations of reliability statistic calculations

Within-Subject Mean \((\mu_w)\)

\(\mu_w\) is the average of all measurements of one eye for a given individual. The overall mean \((\mu)\) is calculated by taking the mean of \(\mu_w\) across the dataset. The overall mean is included in the final table for reference.

\[ \mu_w = \frac{1}{M}\sum_{i=1}^{M} x_i \]

\[\text{where } M \text{ is the number of measurements per eye,}\]

Within-Subject Standard Deviation \((S_w)\)

Find \(S_w\) by first calculating the variance of the measurements per individual eye. The equation below is general for any number of measurements; in this study there are at least 2 measurements per eye, but sometimes more.

\[ \sigma^2_{measurement} = \frac{1}{M}\sum_{i=1}^{M} (x_i - \mu_w)^2 \]

\[ \text{where } M \text{ is the number of measurements per eye} \]

To calculate \(S_w\), average of the variance of measurements \((\sigma^2_{measurement})\) for all eyes measured, then take the square root.

\[ Sw = \sqrt{\frac{1}{N}\sum_{i=1}^{N}\sigma^2_{measurement,i}} \]

\[ \text{where } N \text{ is the number of eyes measured} \]

Within-Subject Coefficient of Repeatability \((CR_w)\)

The \(CR_w\) provides the uncertainty of repeated measures.

\[ CRw = \sqrt2 * 1.96 * Sw \]

The \(CR_w\) can be interpreted as:

“The difference between two measurements for the same subject is expected to be less than [\(CR_w\)] for 95% of pairs of observations.”³

Within-Subject Coefficient of Variation \((CV_w)\)

\[ CVw = 100 *\frac{Sw}{\mu} \]

ICC, One Eye

Intraclass Correlation Coefficient (ICC) is scored using the ICCest() function from the ICC package. This function “estimates the ICC and confidence intervals using the variance components from a one-way ANOVA.”

ICCest() adjusts for repeat measurements on each participant, but not for repeat measurements on both eyes. Therefore, ICC calculations with this function will be done for data from 1 eye per participant.

This is a preliminary result, as we want to calculate the ICC after adjusting for participant and eye (left or right). This will be done later in the mixed effects regression models.

Intra-Visit ICC, One Eye

Normal

OCTA Variable	n_people	ICC	ICC 95% CL	k	varw	vara
Vessel Diameter (units?)	68	0.868	(0.807, 0.913)	2.646	0.059	0.385
Vessel Area Density	68	0.910	(0.867, 0.941)	2.646	0.000	0.002
Vessel Area Density, Zeiss	68	0.935	(0.902, 0.957)	2.646	0.000	0.000
Vessel Skeleton Density (units?)	68	0.914	(0.872, 0.943)	2.646	0.000	0.000
Vessel Perimeter Index (units?)	68	0.911	(0.868, 0.942)	2.646	0.000	0.002
Vessel Complexity Index (units?)	68	0.902	(0.855, 0.936)	2.646	40923.407	375866.654
Flow Impairment Zone (units?)	68	0.863	(0.801, 0.909)	2.646	0.696	4.389
Flux	68	0.914	(0.872, 0.944)	2.646	0.000	0.000
Flux, Zeiss	68	0.930	(0.896, 0.954)	2.646	0.000	0.001

Glaucoma

OCTA Variable	n_people	ICC	ICC 95% CL	k	varw	vara
Vessel Diameter (units?)	81	0.948	(0.924, 0.965)	2.492	0.166	3.028
Vessel Area Density	81	0.905	(0.862, 0.935)	2.492	0.001	0.006
Vessel Area Density, Zeiss	81	0.972	(0.958, 0.981)	2.492	0.000	0.002
Vessel Skeleton Density (units?)	81	0.909	(0.869, 0.939)	2.492	0.000	0.001
Vessel Perimeter Index (units?)	81	0.905	(0.863, 0.936)	2.492	0.001	0.005
Vessel Complexity Index (units?)	81	0.903	(0.860, 0.934)	2.492	145259.846	1347930.822
Flow Impairment Zone (units?)	81	0.877	(0.824, 0.917)	2.492	2.314	16.543
Flux	81	0.898	(0.854, 0.931)	2.492	0.000	0.001
Flux, Zeiss	81	0.965	(0.949, 0.977)	2.492	0.000	0.001

Inter-Visit ICC, One Eye

Inter-Visit ICC Normal

Normal, All

OCTA Variable	n_people	ICC	ICC 95% CL	k	varw	vara
Vessel Diameter (units?)	67	0.738	(0.620, 0.826)	2.251	0.122	0.344
Vessel Area Density	67	0.765	(0.656, 0.845)	2.251	0.001	0.002
Vessel Area Density, Zeiss	67	0.842	(0.763, 0.897)	2.251	0.000	0.000
Vessel Skeleton Density (units?)	67	0.779	(0.675, 0.855)	2.251	0.000	0.000
Vessel Perimeter Index (units?)	67	0.786	(0.685, 0.859)	2.251	0.000	0.002
Vessel Complexity Index (units?)	67	0.772	(0.665, 0.850)	2.251	114021.925	385838.270
Flow Impairment Zone (units?)	67	0.708	(0.580, 0.805)	2.251	2.001	4.862
Flux	67	0.746	(0.630, 0.831)	2.251	0.000	0.000
Flux, Zeiss	67	0.832	(0.749, 0.891)	2.251	0.000	0.001

Normal, 365 Days

OCTA Variable	n_people	ICC	ICC 95% CL	k	varw	vara
Vessel Diameter (units?)	40	0.727	(0.553, 0.843)	2.122	0.138	0.367
Vessel Area Density	40	0.801	(0.664, 0.888)	2.122	0.000	0.002
Vessel Area Density, Zeiss	40	0.871	(0.776, 0.928)	2.122	0.000	0.000
Vessel Skeleton Density (units?)	40	0.803	(0.668, 0.889)	2.122	0.000	0.000
Vessel Perimeter Index (units?)	40	0.800	(0.662, 0.887)	2.122	0.000	0.002
Vessel Complexity Index (units?)	40	0.800	(0.662, 0.887)	2.122	96147.110	383611.238
Flow Impairment Zone (units?)	40	0.729	(0.556, 0.844)	2.122	1.858	5.002
Flux	40	0.800	(0.663, 0.887)	2.122	0.000	0.000
Flux, Zeiss	40	0.877	(0.786, 0.932)	2.122	0.000	0.001

Normal, 180 Days

OCTA Variable	n_people	ICC	ICC 95% CL	k	varw	vara
Vessel Diameter (units?)	19	0.725	(0.455, 0.880)	2.198	0.166	0.437
Vessel Area Density	19	0.674	(0.375, 0.855)	2.198	0.001	0.002
Vessel Area Density, Zeiss	19	0.807	(0.598, 0.918)	2.198	0.000	0.000
Vessel Skeleton Density (units?)	19	0.690	(0.399, 0.863)	2.198	0.000	0.000
Vessel Perimeter Index (units?)	19	0.674	(0.374, 0.855)	2.198	0.001	0.001
Vessel Complexity Index (units?)	19	0.690	(0.399, 0.863)	2.198	148183.011	329773.456
Flow Impairment Zone (units?)	19	0.637	(0.318, 0.836)	2.198	2.723	4.770
Flux	19	0.662	(0.356, 0.849)	2.198	0.000	0.000
Flux, Zeiss	19	0.699	(0.413, 0.867)	2.198	0.000	0.000

Inter-Visit ICC Glaucoma

Glaucoma

OCTA Variable	n_people	ICC	ICC 95% CL	k	varw	vara
Vessel Diameter (units?)	81	0.897	(0.855, 0.930)	2.77	0.364	3.180
Vessel Area Density	81	0.823	(0.755, 0.877)	2.77	0.001	0.005
Vessel Area Density, Zeiss	81	0.959	(0.940, 0.972)	2.77	0.000	0.002
Vessel Skeleton Density (units?)	81	0.834	(0.769, 0.885)	2.77	0.000	0.001
Vessel Perimeter Index (units?)	81	0.824	(0.756, 0.877)	2.77	0.001	0.005
Vessel Complexity Index (units?)	81	0.829	(0.762, 0.881)	2.77	243669.027	1179265.229
Flow Impairment Zone (units?)	81	0.760	(0.673, 0.831)	2.77	4.352	13.816
Flux	81	0.790	(0.711, 0.852)	2.77	0.000	0.001
Flux, Zeiss	81	0.885	(0.838, 0.921)	2.77	0.000	0.001

Glaucoma, 365 Days

OCTA Variable	n_people	ICC	ICC 95% CL	k	varw	vara
Vessel Diameter (units?)	62	0.894	(0.840, 0.932)	2.589	0.411	3.448
Vessel Area Density	62	0.821	(0.738, 0.883)	2.589	0.001	0.006
Vessel Area Density, Zeiss	62	0.956	(0.932, 0.972)	2.589	0.000	0.002
Vessel Skeleton Density (units?)	62	0.833	(0.754, 0.891)	2.589	0.000	0.001
Vessel Perimeter Index (units?)	62	0.823	(0.740, 0.884)	2.589	0.001	0.005
Vessel Complexity Index (units?)	62	0.827	(0.746, 0.887)	2.589	258530.328	1237596.013
Flow Impairment Zone (units?)	62	0.760	(0.655, 0.841)	2.589	4.645	14.744
Flux	62	0.785	(0.689, 0.859)	2.589	0.000	0.001
Flux, Zeiss	62	0.895	(0.842, 0.933)	2.589	0.000	0.001

Glaucoma, 180 Days

OCTA Variable	n_people	ICC	ICC 95% CL	k	varw	vara
Vessel Diameter (units?)	48	0.897	(0.834, 0.939)	2.391	0.447	3.896
Vessel Area Density	48	0.850	(0.761, 0.910)	2.391	0.001	0.006
Vessel Area Density, Zeiss	48	0.951	(0.920, 0.971)	2.391	0.000	0.002
Vessel Skeleton Density (units?)	48	0.861	(0.778, 0.917)	2.391	0.000	0.001
Vessel Perimeter Index (units?)	48	0.851	(0.763, 0.910)	2.391	0.001	0.005
Vessel Complexity Index (units?)	48	0.851	(0.763, 0.910)	2.391	241852.820	1380095.308
Flow Impairment Zone (units?)	48	0.773	(0.650, 0.861)	2.391	4.913	16.772
Flux	48	0.821	(0.719, 0.892)	2.391	0.000	0.001
Flux, Zeiss	48	0.909	(0.852, 0.946)	2.391	0.000	0.001

Calculating ICC Statistic

\[ \text{ICC} = \frac{\text{between}}{\text{between} + \text{within}}\]

“In the output for the random effects model ‘SID’ is the estimated between-group variance, which in the ICCest output is called ‘vara’ (variance among groups). The within-group variance is ‘Residual’ in the random effects model output, while in ICCest it’s called ‘varw.’ You can see that the values for those two variances match perfectly in the two different outputs. The ICC is defined as between/(between+within). That calculation is not part of the random effects model output, but it is part of the ICCest output, along with confidence intervals for the ICC estimate. The ICC are really high for intravisit (around 97%) and a little lower for intervisit (about 94%). If we were to calculate these ICC for glaucoma and controls separately I think they would be significantly lower because of the reduced between-group variability.” - BB 9/4/2019

ARVO Abstract Tables, One Eye

Do not use these tables for the final write-up.

Originally, we submitted the abstract to ARVO after calculating reliability statistics on one, randomly selected eye per person. These are kept in the analysis here just to show what we had previously shown. Now, we have calculated these statistics using both eyes (down below). So when writing the final paper, only include those.

Table 1: Participants

	Overall
n	149
Sociodemographic Variables
age (mean (SD))	56.97 (16.10)
Sex = Male (%)	72 (48.3)
Systemic Clinical Variables
Hypertension Diagnosis = Yes (%)	43 (28.9)
Diabetes Mellitus Diagnosis = Yes (%)	17 (11.4)
Optic Neuropathy = Yes (%)	1 ( 0.7)
Ophthalmic Clinical Variables
Glaucoma Diagnosis, Binary = Glaucoma (%)	81 (54.4)
Glaucoma Diagnosis Laterality, Ordinal (%)
Normal, Bilateral	60 (40.3)
Glaucoma, Bilateral	71 (47.7)
Glaucoma, Unilateral	18 (12.1)
Diabetic Retinopathy Diagnosis, Binary = Yes (%)	4 ( 2.7)
Ophthalmic Surgical Variables
Surgical Procedure for Cataract Extraction = Yes (%)	29 (19.5)
Surgical Procedure for Glaucoma (%)
None	106 (71.1)
Laser	24 (16.1)
Minimally Invasive Glaucoma Surgery	1 ( 0.7)
Filter	18 (12.1)
OCT Angiography Signal Strength
signal_strength (mean (SD))	9.31 (0.75)

Table 2: Reliability Statistics, One Eye

Table 2a: Intra-Visit Repeatability

All data was included for intra-visit repeatability statistics.

Intra-visit repeatability statistics for participants with repeated measurements on the same day:

• Normal (n = 68).

• Glaucoma (n = 81).

OCTA Variable	Mean		ICC				Sw				CRw				CVw
	Normal	Glaucoma	Normal		Glaucoma		Normal		Glaucoma		Normal		Glaucoma		Normal		Glaucoma
var_name_normal	µ_normal	µ_glc	ICC_pretty_normal	ICC_pretty_cl_normal	ICC_pretty_glc	ICC_pretty_cl_glc	Sw_pretty_normal	Sw_pretty_cl_normal	Sw_pretty_glc	Sw_pretty_cl_glc	CRw_pretty_normal	CRw_pretty_cl_normal	CRw_pretty_glc	CRw_pretty_cl_glc	CVw_pretty_normal	CVw_pretty_cl_normal	CVw_pretty_glc	CVw_pretty_cl_glc
Vessel Area Density	0.362	0.278	0.910	(0.867, 0.941)	0.905	(0.862, 0.935)	0.014	(0.014, 0.014)	0.024	(0.024, 0.025)	0.038	(0.038, 0.039)	0.068	(0.067, 0.068)	3.832	(3.820, 3.843)	8.783	(8.684, 8.883)
Vessel Area Density, Zeiss	0.429	0.397	0.935	(0.902, 0.957)	0.972	(0.958, 0.981)	0.006	(0.006, 0.006)	0.007	(0.007, 0.007)	0.016	(0.016, 0.016)	0.019	(0.019, 0.019)	1.369	(1.368, 1.371)	1.767	(1.765, 1.770)
Vessel Skeleton Density (units?)	0.146	0.108	0.914	(0.872, 0.943)	0.909	(0.869, 0.939)	0.006	(0.006, 0.006)	0.011	(0.011, 0.011)	0.017	(0.017, 0.017)	0.030	(0.029, 0.030)	4.215	(4.210, 4.221)	9.857	(9.809, 9.904)
Flux	0.130	0.096	0.914	(0.872, 0.944)	0.898	(0.854, 0.931)	0.006	(0.006, 0.006)	0.010	(0.010, 0.010)	0.017	(0.017, 0.017)	0.027	(0.027, 0.027)	4.673	(4.668, 4.679)	10.108	(10.060, 10.156)
Flux, Zeiss	0.360	0.320	0.930	(0.896, 0.954)	0.965	(0.949, 0.977)	0.007	(0.007, 0.007)	0.007	(0.007, 0.007)	0.018	(0.018, 0.018)	0.019	(0.019, 0.019)	1.847	(1.844, 1.849)	2.119	(2.116, 2.122)

Table 2b: Inter-Visit Reproducibility

Data was restricted to 1 year for inter-visits that occurred on different days. This was to avoid changes in eyes over a long amount of time.

Inter-visit reproducibility statistics for participants with repeated measurements within a 1 year window

• Normal (n = 40).

• Glaucoma (n = 62).

OCTA Variable	Mean		ICC				Sw				CRw				CVw
	Normal	Glaucoma	Normal		Glaucoma		Normal		Glaucoma		Normal		Glaucoma		Normal		Glaucoma
var_name_normal	µ_normal	µ_glc	ICC_pretty_normal	ICC_pretty_cl_normal	ICC_pretty_glc	ICC_pretty_cl_glc	Sw_pretty_normal	Sw_pretty_cl_normal	Sw_pretty_glc	Sw_pretty_cl_glc	CRw_pretty_normal	CRw_pretty_cl_normal	CRw_pretty_glc	CRw_pretty_cl_glc	CVw_pretty_normal	CVw_pretty_cl_normal	CVw_pretty_glc	CVw_pretty_cl_glc
Vessel Area Density	0.361	0.260	0.801	(0.664, 0.888)	0.821	(0.738, 0.883)	0.022	(0.022, 0.022)	0.032	(0.032, 0.032)	0.062	(0.061, 0.062)	0.089	(0.088, 0.090)	6.155	(6.102, 6.208)	12.291	(12.155, 12.426)
Vessel Area Density, Zeiss	0.428	0.390	0.871	(0.776, 0.928)	0.956	(0.932, 0.972)	0.008	(0.008, 0.008)	0.009	(0.009, 0.009)	0.023	(0.023, 0.023)	0.025	(0.025, 0.025)	1.961	(1.957, 1.966)	2.315	(2.312, 2.319)
Vessel Skeleton Density (units?)	0.146	0.100	0.803	(0.668, 0.889)	0.833	(0.754, 0.891)	0.010	(0.010, 0.010)	0.014	(0.014, 0.014)	0.028	(0.028, 0.028)	0.038	(0.038, 0.038)	6.871	(6.846, 6.895)	13.783	(13.718, 13.848)
Flux	0.129	0.090	0.800	(0.663, 0.887)	0.785	(0.689, 0.859)	0.010	(0.010, 0.010)	0.013	(0.013, 0.013)	0.027	(0.027, 0.027)	0.036	(0.036, 0.037)	7.568	(7.537, 7.598)	14.641	(14.571, 14.710)
Flux, Zeiss	0.358	0.314	0.877	(0.786, 0.932)	0.895	(0.842, 0.933)	0.010	(0.010, 0.010)	0.011	(0.011, 0.011)	0.029	(0.029, 0.029)	0.031	(0.031, 0.031)	2.900	(2.888, 2.912)	3.586	(3.579, 3.593)

Mixed Models, Both Eyes

Mixed Effects Regression Models allow random effects for certain variables. This allows us to include multiple measurements from the same person and eye while still satisfying independence.

Figure 1

Here are the Bland Altman Plots for OCTA outcomes in both eyes. The variables of interest are VAD and FLUX for the current algorithm and the Zeiss algorithm. This is an interesting plot to show before explaing the mixed effects model.

## quartz_off_screen 
##                 3

## quartz_off_screen 
##                 2

## quartz_off_screen 
##                 3

## quartz_off_screen 
##                 2

Adjusting for Patients

This model has a random effect for the participant ID, which accounts for repeated measurements on the same person. This does not, however, account for measurements on more than one eye per person. Therefore the data was used that randomly selected one eye per participant. Later models will adjust for this.

This should produce the same ICC and other reliability statistics as the ICCest() function in the tables above. These were not calculated out to compare. Just one model is shown for explanation.

## Linear mixed model fit by REML. t-tests use Satterthwaite's method [
## lmerModLmerTest]
## Formula: v_area_density ~ (1 | ptid)
##    Data: data_octa_global_intra_1eye
## 
## REML criterion at convergence: -1324.1
## 
## Scaled residuals: 
##     Min      1Q  Median      3Q     Max 
## -4.6651 -0.3773 -0.0203  0.3606  4.7125 
## 
## Random effects:
##  Groups   Name        Variance  Std.Dev.
##  ptid     (Intercept) 0.0062447 0.07902 
##  Residual             0.0004409 0.02100 
## Number of obs: 382, groups:  ptid, 149
## 
## Fixed effects:
##              Estimate Std. Error        df t value Pr(>|t|)    
## (Intercept) 3.130e-01  6.566e-03 1.477e+02   47.66   <2e-16 ***
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1

Adjusting for Both Eyes and Patients

Linear, mixed-effects modeling was used to account for repeated measurements on both eyes of each participant. This allows random effects for both the patient and the eye (left or right), allowing us to model the ICC and other reliability statistics without violating independence.

## Linear mixed model fit by REML. t-tests use Satterthwaite's method [
## lmerModLmerTest]
## Formula: v_area_density ~ (1 | ptid/eyeid)
##    Data: data_octa_global_intra_2eye
## 
## REML criterion at convergence: -2370.7
## 
## Scaled residuals: 
##     Min      1Q  Median      3Q     Max 
## -4.8268 -0.3850 -0.0216  0.3809  4.9207 
## 
## Random effects:
##  Groups     Name        Variance  Std.Dev.
##  eyeid:ptid (Intercept) 0.0013947 0.03735 
##  ptid       (Intercept) 0.0050627 0.07115 
##  Residual               0.0004008 0.02002 
## Number of obs: 644, groups:  eyeid:ptid, 244; ptid, 149
## 
## Fixed effects:
##              Estimate Std. Error        df t value Pr(>|t|)    
## (Intercept) 3.118e-01  6.399e-03 1.457e+02   48.73   <2e-16 ***
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1

Table 3: Reliability Statistics, Both Eyes

Table 3a: Both Eyes, Intra-Visit Repeatability

OCTA Variable	N Participants		Mean		ICC				Sw				CRw				CVw
	Normal	Glaucoma	Normal	Glaucoma	Normal		Glaucoma		Normal		Glaucoma		Normal		Glaucoma		Normal		Glaucoma
var_name	pretty_n_participant_normal	pretty_n_participant_glaucoma	pretty_mu_normal	pretty_mu_glaucoma	pretty_icc_normal	pretty_icc_cl_normal	pretty_icc_glaucoma	pretty_icc_cl_glaucoma	pretty_sw_normal	pretty_sw_cl_normal	pretty_sw_glaucoma	pretty_sw_cl_glaucoma	pretty_crw_normal	pretty_crw_cl_normal	pretty_crw_glaucoma	pretty_crw_cl_glaucoma	pretty_cvw_normal	pretty_cvw_cl_normal	pretty_cvw_glaucoma	pretty_cvw_cl_glaucoma
Vessel Area Density	73	86	0.362	0.279	0.924	(0.890, 0.947)	0.914	(0.884, 0.934)	0.015	(0.014, 0.017)	0.024	(0.022, 0.026)	0.042	(0.039, 0.047)	0.066	(0.061, 0.075)	4.214	(3.847, 4.559)	8.602	(7.474, 9.513)
Vessel Area Density, Zeiss	73	86	0.430	0.398	0.935	(0.905, 0.950)	0.971	(0.962, 0.979)	0.006	(0.006, 0.007)	0.007	(0.006, 0.007)	0.018	(0.016, 0.019)	0.018	(0.017, 0.020)	1.471	(1.326, 1.592)	1.670	(1.500, 1.828)
Vessel Skeleton Density (units?)	73	86	0.146	0.108	0.921	(0.887, 0.945)	0.919	(0.889, 0.939)	0.007	(0.006, 0.007)	0.010	(0.009, 0.012)	0.019	(0.017, 0.021)	0.029	(0.027, 0.032)	4.756	(4.336, 5.218)	9.570	(8.814, 10.370)
Flux	73	86	0.130	0.096	0.920	(0.887, 0.942)	0.910	(0.866, 0.934)	0.007	(0.006, 0.008)	0.009	(0.009, 0.010)	0.019	(0.017, 0.021)	0.026	(0.024, 0.030)	5.238	(4.814, 5.714)	9.866	(8.802, 10.779)
Flux, Zeiss	73	86	0.359	0.320	0.942	(0.916, 0.957)	0.959	(0.944, 0.969)	0.007	(0.006, 0.008)	0.007	(0.007, 0.008)	0.020	(0.017, 0.021)	0.020	(0.018, 0.022)	1.978	(1.784, 2.161)	2.258	(2.030, 2.474)

Table 3b: Both Eyes, Inter-Visit Reproducibility

Look at data by different time restrictions, to see if the ICC increases as the window of time shortens.

**I recommend we use the one that restricts to a single year (365 Days), in spite of the singularity warning. I included all possibilities for reference, however.

All

OCTA Variable	N Participants		Mean		ICC				Sw				CRw				CVw
	Normal	Glaucoma	Normal	Glaucoma	Normal		Glaucoma		Normal		Glaucoma		Normal		Glaucoma		Normal		Glaucoma
var_name	pretty_n_participant_normal	pretty_n_participant_glaucoma	pretty_mu_normal	pretty_mu_glaucoma	pretty_icc_normal	pretty_icc_cl_normal	pretty_icc_glaucoma	pretty_icc_cl_glaucoma	pretty_sw_normal	pretty_sw_cl_normal	pretty_sw_glaucoma	pretty_sw_cl_glaucoma	pretty_crw_normal	pretty_crw_cl_normal	pretty_crw_glaucoma	pretty_crw_cl_glaucoma	pretty_cvw_normal	pretty_cvw_cl_normal	pretty_cvw_glaucoma	pretty_cvw_cl_glaucoma
Vessel Area Density	72	86	0.361	0.271	0.816	(0.730, 0.874)	0.819	(0.743, 0.853)	0.024	(0.021, 0.026)	0.035	(0.032, 0.038)	0.067	(0.060, 0.073)	0.098	(0.089, 0.106)	6.689	(5.954, 7.428)	13.043	(11.967, 14.141)
Vessel Area Density, Zeiss	72	86	0.431	0.393	0.872	(0.825, 0.908)	0.951	(0.931, 0.968)	0.009	(0.008, 0.010)	0.009	(0.008, 0.010)	0.025	(0.022, 0.027)	0.024	(0.022, 0.026)	2.058	(1.806, 2.309)	2.232	(2.027, 2.392)
Vessel Skeleton Density (units?)	72	86	0.145	0.105	0.816	(0.750, 0.865)	0.828	(0.767, 0.875)	0.011	(0.010, 0.012)	0.015	(0.014, 0.017)	0.030	(0.026, 0.033)	0.042	(0.039, 0.045)	7.356	(6.527, 8.062)	14.501	(13.435, 15.951)
Flux	72	86	0.129	0.094	0.803	(0.709, 0.850)	0.786	(0.712, 0.843)	0.011	(0.010, 0.012)	0.015	(0.013, 0.016)	0.030	(0.026, 0.034)	0.041	(0.038, 0.045)	8.486	(7.684, 9.574)	15.744	(14.203, 17.260)
Flux, Zeiss	72	86	0.358	0.318	0.850	(0.798, 0.897)	0.894	(0.855, 0.919)	0.012	(0.010, 0.013)	0.012	(0.011, 0.013)	0.032	(0.028, 0.036)	0.032	(0.030, 0.035)	3.276	(2.873, 3.645)	3.689	(3.345, 3.973)

365 Days

## boundary (singular) fit: see ?isSingular

OCTA Variable	N Participants		Mean		ICC				Sw				CRw				CVw
	Normal	Glaucoma	Normal	Glaucoma	Normal		Glaucoma		Normal		Glaucoma		Normal		Glaucoma		Normal		Glaucoma
var_name	pretty_n_participant_normal	pretty_n_participant_glaucoma	pretty_mu_normal	pretty_mu_glaucoma	pretty_icc_normal	pretty_icc_cl_normal	pretty_icc_glaucoma	pretty_icc_cl_glaucoma	pretty_sw_normal	pretty_sw_cl_normal	pretty_sw_glaucoma	pretty_sw_cl_glaucoma	pretty_crw_normal	pretty_crw_cl_normal	pretty_crw_glaucoma	pretty_crw_cl_glaucoma	pretty_cvw_normal	pretty_cvw_cl_normal	pretty_cvw_glaucoma	pretty_cvw_cl_glaucoma
Vessel Area Density	44	67	0.364	0.266	0.793	(0.704, 0.860)	0.838	(0.773, 0.883)	0.024	(0.020, 0.027)	0.034	(0.031, 0.037)	0.067	(0.058, 0.077)	0.094	(0.084, 0.104)	6.608	(5.475, 7.663)	12.691	(11.331, 14.131)
Vessel Area Density, Zeiss	44	67	0.430	0.393	0.859	(0.769, 0.913)	0.955	(0.932, 0.972)	0.009	(0.007, 0.010)	0.009	(0.008, 0.010)	0.024	(0.020, 0.028)	0.024	(0.022, 0.026)	1.996	(1.684, 2.290)	2.191	(1.941, 2.455)
Vessel Skeleton Density (units?)	44	67	0.147	0.103	0.791	(0.669, 0.848)	0.849	(0.783, 0.888)	0.011	(0.009, 0.013)	0.014	(0.013, 0.016)	0.030	(0.025, 0.034)	0.040	(0.036, 0.044)	7.313	(6.056, 8.773)	14.057	(12.494, 15.492)
Flux	44	67	0.131	0.092	0.801	(0.678, 0.879)	0.806	(0.727, 0.864)	0.011	(0.009, 0.012)	0.014	(0.013, 0.016)	0.029	(0.025, 0.033)	0.039	(0.035, 0.043)	8.079	(6.567, 9.712)	15.326	(13.804, 17.218)
Flux, Zeiss	44	67	0.360	0.317	0.864	(0.801, 0.918)	0.913	(0.871, 0.939)	0.011	(0.009, 0.013)	0.011	(0.010, 0.012)	0.031	(0.026, 0.035)	0.030	(0.027, 0.033)	3.095	(2.502, 3.439)	3.429	(3.083, 3.822)

180 Days

## boundary (singular) fit: see ?isSingular

OCTA Variable	N Participants		Mean		ICC				Sw				CRw				CVw
	Normal	Glaucoma	Normal	Glaucoma	Normal		Glaucoma		Normal		Glaucoma		Normal		Glaucoma		Normal		Glaucoma
var_name	pretty_n_participant_normal	pretty_n_participant_glaucoma	pretty_mu_normal	pretty_mu_glaucoma	pretty_icc_normal	pretty_icc_cl_normal	pretty_icc_glaucoma	pretty_icc_cl_glaucoma	pretty_sw_normal	pretty_sw_cl_normal	pretty_sw_glaucoma	pretty_sw_cl_glaucoma	pretty_crw_normal	pretty_crw_cl_normal	pretty_crw_glaucoma	pretty_crw_cl_glaucoma	pretty_cvw_normal	pretty_cvw_cl_normal	pretty_cvw_glaucoma	pretty_cvw_cl_glaucoma
Vessel Area Density	23	52	0.367	0.264	0.702	(0.486, 0.840)	0.883	(0.807, 0.918)	0.030	(0.023, 0.038)	0.030	(0.026, 0.034)	0.083	(0.065, 0.100)	0.084	(0.075, 0.095)	8.193	(6.097, 9.811)	11.459	(9.826, 12.968)
Vessel Area Density, Zeiss	23	52	0.434	0.394	0.833	(0.690, 0.907)	0.954	(0.932, 0.966)	0.009	(0.007, 0.011)	0.009	(0.008, 0.010)	0.024	(0.019, 0.028)	0.025	(0.022, 0.028)	1.971	(1.557, 2.465)	2.273	(2.034, 2.547)
Vessel Skeleton Density (units?)	23	52	0.149	0.102	0.701	(0.512, 0.833)	0.891	(0.832, 0.926)	0.014	(0.011, 0.017)	0.013	(0.011, 0.015)	0.038	(0.029, 0.046)	0.036	(0.031, 0.040)	9.073	(7.318, 11.147)	12.684	(10.938, 14.644)
Flux	23	52	0.131	0.092	0.718	(0.469, 0.821)	0.864	(0.788, 0.912)	0.013	(0.010, 0.015)	0.012	(0.011, 0.014)	0.036	(0.029, 0.043)	0.034	(0.029, 0.038)	9.871	(8.124, 12.048)	13.525	(11.240, 15.904)
Flux, Zeiss	23	52	0.358	0.315	0.765	(0.570, 0.863)	0.923	(0.875, 0.950)	0.014	(0.011, 0.017)	0.011	(0.010, 0.013)	0.038	(0.030, 0.044)	0.031	(0.028, 0.035)	3.815	(3.140, 4.306)	3.522	(3.103, 3.971)

Signal Strength, Both Eyes

We take for granted that signal strength affects the OCTA outcome variables. But we should still show this formally, as Venugopal 2018 has at the end of their paper.

“Signal strength index values of the scans had a significant effect on the repeatability of OCTA with the vessel density values increasing in scans with higher SSI values.”²

Their result is a simple table of regression estimates for signal strength, shown in the output below. We’re really showing here that SS is important to include as a covariate in measurements that use OCTA.

Linear Mixed Effects Model

This is an example of the LME Model used to calculate coefficients in the table below

## Linear mixed model fit by REML. t-tests use Satterthwaite's method [
## lmerModLmerTest]
## Formula: v_area_density ~ signal_strength + (1 | ptid/eyeid)
##    Data: data_octa_global_intra_2eye
## 
## REML criterion at convergence: -2437.3
## 
## Scaled residuals: 
##     Min      1Q  Median      3Q     Max 
## -5.1815 -0.3513 -0.0318  0.3754  5.2588 
## 
## Random effects:
##  Groups     Name        Variance  Std.Dev.
##  eyeid:ptid (Intercept) 0.0013550 0.03681 
##  ptid       (Intercept) 0.0044108 0.06641 
##  Residual               0.0003494 0.01869 
## Number of obs: 644, groups:  eyeid:ptid, 244; ptid, 149
## 
## Fixed effects:
##                  Estimate Std. Error        df t value Pr(>|t|)    
## (Intercept)     1.601e-01  1.776e-02 5.612e+02   9.016   <2e-16 ***
## signal_strength 1.634e-02  1.798e-03 4.763e+02   9.089   <2e-16 ***
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## 
## Correlation of Fixed Effects:
##             (Intr)
## sgnl_strngt -0.941

Signal Strength Affects Reliability of OCTA Measurements

Overall

octa_outcome	parameter	pretty_beta	pretty_se	pretty_cl	pretty_pval
v_area_density	signal_strength	0.016	0.002	(0.013, 0.020)	0.000
zeiss_v_area_density	signal_strength	0.005	0.001	(0.004, 0.006)	0.000
v_skeleton_density	signal_strength	0.007	0.001	(0.005, 0.009)	0.000
flux	signal_strength	0.007	0.001	(0.005, 0.008)	0.000
zeiss_flux	signal_strength	0.008	0.001	(0.007, 0.009)	0.000

Normal

octa_outcome	parameter	pretty_beta	pretty_se	pretty_cl	pretty_pval
v_area_density	signal_strength	0.013	0.002	(0.009, 0.017)	0.000
zeiss_v_area_density	signal_strength	0.005	0.001	(0.003, 0.006)	0.000
v_skeleton_density	signal_strength	0.006	0.001	(0.004, 0.007)	0.000
flux	signal_strength	0.006	0.001	(0.004, 0.008)	0.000
zeiss_flux	signal_strength	0.007	0.001	(0.006, 0.009)	0.000

Glaucoma

octa_outcome	parameter	pretty_beta	pretty_se	pretty_cl	pretty_pval
v_area_density	signal_strength	0.019	0.003	(0.013, 0.025)	0.000
zeiss_v_area_density	signal_strength	0.005	0.001	(0.003, 0.006)	0.000
v_skeleton_density	signal_strength	0.008	0.001	(0.005, 0.011)	0.000
flux	signal_strength	0.007	0.001	(0.005, 0.009)	0.000
zeiss_flux	signal_strength	0.008	0.001	(0.006, 0.010)	0.000

References

1. Venugopal JP, Rao HL, Weinreb RN, et al. Repeatability and comparability of peripapillary vessel density measurements of high-density and non-high-density optical coherence tomography angiography scans in normal and glaucoma eyes. The British Journal of Ophthalmology 2019;103:949–954.

2. Venugopal JP, Rao HL, Weinreb RN, et al. Repeatability of vessel density measurements of optical coherence tomography angiography in normal and glaucoma eyes. The British Journal of Ophthalmology 2018;102:352–357.

3. Bland JM, Altman DG. Statistics Notes: Measurement error. BMJ : British Medical Journal 1996;313:744.